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Effect of α-cyperone on H2O2-induced neurotoxicity in SH-SY5Y cells. After being pretreated with α-cyperone (15 or 30 μM) for 2 h, SH-SY5Y cells were stimulated with H2O2 (200 μM) for 24 h. (A) Cell viability was measured by MTT assay. (B) The release of LDH was assessed by LDH assay. All experiments were repeated at least three times and similar results were obtained. Data are presented as the mean ± SE, (n = 5 samples per group). ##p < 0.01 vs. the control group, *p < 0.05 and **p < 0.01 vs. the H2O2-treated group.
Source publication
α-Cyperone, extracted from Cyperus rotundus, has been reported to inhibit microglia-mediated neuroinflammation. Oxidative stress and apoptosis play crucial roles in the course of Parkinson’s disease (PD). PD is a common neurodegenerative disease characterized by selective death of dopaminergic neurons. This study was designed to investigate the neu...
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Objectives
Astragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson’s disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD.
Materials and Methods
SH-SY5Y cells were incubated...
Citations
... Additionally, knowing the regulatory mechanisms that regulate cells, ROS in particular locations within the cell is essential for figuring out their role in cell signaling [41]. The particular intracellular locations where ROS are controlled include the mitochondria and endosomes, which are significant ROS damage targets and participate in the control of apoptosis by oxidizing mitochondria pores (Figures 1-3) [43]. ...
... As an adapter protein, Kelch-like ECH-associated protein 1 interacts with nuclear factor erythroid 2-related factor 2 to function [45]. Under normal circumstances, Keap 1 controls the ubiquitin-protease system that breaks down Nrf2 in order to stop the transcriptional activation of antioxidant response elements [43]. However, in conditions of oxidative stress, Keap1 experiences conformational changes that stabilize its association with Nrf2, halting its deterioration and enabling Nrf2 to go to the nucleus [43]. ...
... Under normal circumstances, Keap 1 controls the ubiquitin-protease system that breaks down Nrf2 in order to stop the transcriptional activation of antioxidant response elements [43]. However, in conditions of oxidative stress, Keap1 experiences conformational changes that stabilize its association with Nrf2, halting its deterioration and enabling Nrf2 to go to the nucleus [43]. After entering the nucleus, Nrf2 binds to antioxidant response elements in the target genes' promoter regions, causing antioxidant enzymes and other cytoprotective proteins to begin to be transcribed [44]. ...
Rheumatoid arthritis (RA) is a chronic and debilitating inflammatory condition characterized by joint degradation and permanent disability. Excessive production of reactive oxygen species (ROS) is implicated in RA pathogenesis, leading to oxidative stress and tissue damage. In recent years, nano-particles have emerged as promising carriers for ROS regulation therapies in RA treatment. This review explores the interplay between ROS and RA, emphasizing the importance of cell signaling pathways in ROS control. The potential of nano-particles as targeted drug delivery systems to scavenge excess ROS and restore redox equilibrium within affected cells is discussed. Preclinical studies using ROS-neutralizing nano-particles in RA animal models have shown significant reductions in joint inflammation and cartilage degradation. Clinical trials have further validated the safety and efficacy of nano-particle treatments in RA patients, leading to improved disease activity and joint function. The review highlights the benefits of nano-particle-based ROS control therapies, including improved drug solubility, prolonged drug delivery, reduced systemic side effects, and enhanced specificity for inflamed joints. However, further research is needed to fully understand the intricate mechanisms of ROS management in RA and optimize nano-particle production and delivery. Overall, nano-particle-based ROS control therapy holds great promise for revolutionizing RA treatment and improving the quality of life for affected individuals.
... They are the largest class of compounds that have been isolated from this herb (Figs. 3, 4, 5, 6, 7, 8, Table 1). Previous chemical investigation revealed that sesquiterpenes are the most abundant subclass of secondary metabolites derived from this plant species [6,8,9,11,31,[83][84][85][86][87][88][89][90]. ...
... H 2 O 2 and the rise in ROS are related in this process, demonstrating the H 2 O 2 molecule's critical function in the pathophysiology of AD. [268] H 2 O 2 kills cells by apoptosis, as established by a number of in vitro models using CNS neurons that had been isolated or immortalized cell lines. [270][271][272][273][274] One of the most popular cell lines is the human neuroblastoma SH-SY5Y, [270,275] which was developed in 1970 from a biopsy metastatic tumor. Their most crucial traits are their capacity to differentiate into specialized neurons through markers and to have a mixed culture (adherent and in suspension), making adrenergic, cholinergic, and dopaminergic models a fundamental model for the study of neurodegenerative disorders like AD. [276,277] Lately, Angeloni et al. [278] assessed the antioxidant and anti-inflammatory effects of coffee grounds (CG) extracts in aqueous, methanolic, and ethanolic solutions on SH-SY5Y cells. ...
... H 2 O 2 and the rise in ROS are related in this process, demonstrating the H 2 O 2 molecule's critical function in the pathophysiology of AD. [268] H 2 O 2 kills cells by apoptosis, as established by a number of in vitro models using CNS neurons that had been isolated or immortalized cell lines. [270][271][272][273][274] One of the most popular cell lines is the human neuroblastoma SH-SY5Y, [270,275] which was developed in 1970 from a biopsy metastatic tumor. Their most crucial traits are their capacity to differentiate into specialized neurons through markers and to have a mixed culture (adherent and in suspension), making adrenergic, cholinergic, and dopaminergic models a fundamental model for the study of neurodegenerative disorders like AD. [276,277] Lately, Angeloni et al. [278] assessed the antioxidant and anti-inflammatory effects of coffee grounds (CG) extracts in aqueous, methanolic, and ethanolic solutions on SH-SY5Y cells. ...
... On the opposite side, Bcl-2 is an anti-apoptotic protein that promotes mitochondrial membrane stabilization and inhibits the release of apoptogenic factors [46]. In the present study, H 2 O 2 treatment upregulated BAX and cleaved caspase-3 expression, downregulated Bcl-2 expression, and reduced Akt phosphorylation in SH-SY5Y cells, of which the findings are consistent with previous studies [47,48]. However, these changes were significantly blunted in the presence of CI, proposing that CI may protect neuronal cell apoptosis by inhibiting mitochondrial damage-associated apoptotic regulators activated by oxidative stress. ...
... As an adaptive cellular response to ROS accumulation and oxidative stress, Nrf2 is activated and induces the transcription of several antioxidant enzymes [13]. Several studies have shown that the activation of the Nrf2 signaling pathway is mainly responsible for neuroprotective effects from cytotoxic damage [47]. Additionally, we have previously shown that cofilin knockdown increases the expression of Nrf2 and HO-1 in hemin-treated microglial cells [24]. ...
Microglial activation and failure of the antioxidant defense mechanisms are major hallmarks in different brain injuries, particularly traumatic brain injury (TBI). Cofilin is a cytoskeleton-associated protein involved in actin binding and severing. In our previous studies, we identified the putative role of cofilin in mediating microglial activation and apoptosis in ischemic and hemorrhagic conditions.
Others have highlighted the involvement of cofilin in ROS production and the resultant neuronal death; however, more studies are needed to delineate the role of cofilin in oxidative stress conditions. The present study aims to investigate the cellular and molecular effects of cofilin in TBI using both in vitro and in vivo models as well as the first-in-class small-molecule cofilin inhibitor (CI). An in vitro
H2O2-induced oxidative stress model was used in two different types of cells, human neuroblastoma (SH-SY5Y) and microglia (HMC3), along with an in vivo controlled cortical impact model of TBI. Our results show that treatment with H2O2
increases the expression of cofilin and slingshot-1 (SSH-1), an upstream regulator of cofilin, in microglial cells, which was significantly reduced in the CI-treated
group. Cofilin inhibition significantly attenuated H2O2-induced microglial activation by reducing the release of proinflammatory mediators. Furthermore, we demonstrate that CI protects against H2O2-induced ROS accumulation and neuronal cytotoxicity, activates the AKT signaling pathway by increasing its phosphorylation, and modulates mitochondrial-related apoptogenic factors. The expression of NF-E2-related factor 2 (Nrf2) and its associated antioxidant enzymes were also increased
in CI-treated SY-SY5Y. In the mice model of TBI, CI significantly activated the Nrf2 and reduced the expression of oxidative/nitrosative stress markers at the protein and gene levels. Together, our data suggest that cofilin inhibition provides a neuroprotective effect in vitro and in vivo TBI mice models by inhibiting oxidative stress and inflammatory responses, the pivotal mechanisms involved in TBI-induced brain damage.
... On the opposite side, Bcl-2 is an anti-apoptotic protein that promotes mitochondrial membrane stabilization and inhibits the release of apoptogenic factors [46]. In the present study, H 2 O 2 treatment upregulated BAX and cleaved caspase-3 expression, downregulated Bcl-2 expression, and reduced Akt phosphorylation in SH-SY5Y cells, of which the findings are consistent with previous studies [47,48]. However, these changes were significantly blunted in the presence of CI, proposing that CI may protect neuronal cell apoptosis by inhibiting mitochondrial damage-associated apoptotic regulators activated by oxidative stress. ...
... As an adaptive cellular response to ROS accumulation and oxidative stress, Nrf2 is activated and induces the transcription of several antioxidant enzymes [13]. Several studies have shown that the activation of the Nrf2 signaling pathway is mainly responsible for neuroprotective effects from cytotoxic damage [47]. Additionally, we have previously shown that cofilin knockdown increases the expression of Nrf2 and HO-1 in hemin-treated microglial cells [24]. ...
Microglial activation and failure of the antioxidant defense mechanisms are major hallmarks in different brain injuries, particularly traumatic brain injury (TBI). Cofilin is a cytoskeleton-associated protein involved in actin binding and severing. In our previous studies, we identified the putative role of cofilin in mediating microglial activation and apoptosis in ischemic and hemorrhagic conditions. Others have highlighted the involvement of cofilin in ROS production and the resultant neuronal
death; however, more studies are needed to delineate the role of cofilin in oxidative stress conditions. The present study aims to investigate the cellular and molecular effects of cofilin in TBI using both in vitro and in vivo models as well as the first-in-class small-molecule cofilin inhibitor (CI). An in vitro H2O2-induced oxidative stress model was used in two different types of cells, human neuroblastoma (SH-SY5Y) and microglia (HMC3), along with an in vivo controlled cortical impact model of TBI.
Our results show that treatment with H2O2 increases the expression of cofilin and slingshot-1 (SSH-1), an upstream regulator of cofilin, in microglial cells, which was significantly reduced in the CI-treated group. Cofilin inhibition significantly attenuated H2O2-induced microglial activation by reducing the release of proinflammatory mediators. Furthermore, we demonstrate that CI protects against
H2O2 -induced ROS accumulation and neuronal cytotoxicity, activates the AKT signaling pathway by increasing its phosphorylation, and modulates mitochondrial-related apoptogenic factors. The expression of NF-E2-related factor 2 (Nrf2) and its associated antioxidant enzymes were also increased
in CI-treated SY-SY5Y. In the mice model of TBI, CI significantly activated the Nrf2 and reduced
the expression of oxidative/nitrosative stress markers at the protein and gene levels. Together, our data suggest that cofilin inhibition provides a neuroprotective effect in vitro and in vivo TBI mice models by inhibiting oxidative stress and inflammatory responses, the pivotal mechanisms involved in TBI-induced brain damage.
... Various in vitro models carried out with neurons isolated from the CNS and/or with immortalized cell lines, demonstrated that H 2 O 2 causes cell death through apoptosis [118,[131][132][133][134][135]. The human neuroblastoma SH-SY5Y is among the most used cell lines [131,[136][137][138][139][140][141][142], a subclone of a parental neuronal line SK-N-SH, which originated in 1970 from a biopsy metastatic tumor. ...
... Various in vitro models carried out with neurons isolated from the CNS and/or with immortalized cell lines, demonstrated that H 2 O 2 causes cell death through apoptosis [118,[131][132][133][134][135]. The human neuroblastoma SH-SY5Y is among the most used cell lines [131,[136][137][138][139][140][141][142], a subclone of a parental neuronal line SK-N-SH, which originated in 1970 from a biopsy metastatic tumor. Their most important characteristics are their ability to have a mixed culture (adherent and in suspension) and to differentiate into specialized neurons through markers, allowing adrenergic, cholinergic, and dopaminergic models [142,143], to be a basic model for the study of neurodegenerative pathologies, such as AD. ...
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a tangle-shaped accumulation of beta-amyloid peptide fragments and Tau protein in brain neurons. The pathophysiological mechanism involves the presence of Aβ-amyloid peptide, Tau protein, oxidative stress, and an exacerbated neuro-inflammatory response. This review aims to offer an updated compendium of the most recent and promising advances in AD treatment through the administration of phytochemicals. The literature survey was carried out by electronic search in the following specialized databases PubMed/Medline, Embase, TRIP database, Google Scholar, Wiley, and Web of Science regarding published works that included molecular mechanisms and signaling pathways targeted by phytochemicals in various experimental models of Alzheimer’s disease in vitro and in vivo. The results of the studies showed that the use of phytochemicals against AD has gained relevance due to their antioxidant, anti-neuroinflammatory, anti-amyloid, and anti-hyperphosphorylation properties of Tau protein. Some bioactive compounds from plants have been shown to have the ability to prevent and stop the progression of Alzheimer’s.
... In lipopolysaccharide-(LPS-) treated macrophages, α-cyperone exerts its anti-inflammatory effects by inactivating NF-κB to downregulate COX-2 and IL-6 [7]. α-Cyperone bridles apoptosis, oxidative stress, and mitochondrial dysfunction in H 2 O 2treated SH-SY5Y cells through activation of Nrf2 [8]. Nevertheless, α-cyperone's mechanism of action in oxygen and glucose deprivation-(OGD-) induced myocardial injury remains unclear. ...
Objective:
This study is aimed at investigating the mechanism of α-cyperone in oxygen and glucose deprivation- (OGD-) induced myocardial injury.
Methods:
Cardiomyocytes were exposed to OGD and then treated with α-cyperone. The cell counting kit-8 (CCK-8) assay and flow cytometry were performed to determine cell proliferation and apoptosis, respectively. The expression of inflammatory factors was monitored by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The profiles of apoptosis-related proteins, inflammatory proteins, and the Akt/FOXO3a/NF-κB pathway were determined by western blot. The phosphorylation of Akt, FOXO3a, and NF-κB was determined by immunofluorescence assay. The superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content were gauged by the colorimetric method, and the reactive oxygen species (ROS) content was measured.
Results:
α-Cyperone hindered OGD-induced inflammation, oxidative stress, and apoptosis in cardiomyocytes. OGD activated the FOXO3a/NF-κB pathway and hampered the Akt phosphorylation. α-cyperone reversed OGD-mediated FOXO3a/NF-κB pathway activation. Treatment with MK-2206 abated the protective effect of α-cyperone against OGD-induced myocardial injury. The addition of α-cyperone to cardiomyocytes following Bay11-7082 treatment had no conspicuous effect on the viability and apoptosis.
Conclusions:
α-Cyperone protected cardiomyocytes against OGD-induced inflammation and oxidative stress via the Akt/FOXO3a/NF-κB axis.
... An essential oil containing α-Cyperone extracted from rhizome of Cyperus rotundus seem to possess beneficial properties such as protecting host cells from lipopolysaccharide mediated cellular damage and from H 2 O 2 -induced oxidative stress and apoptosis in neuronal cells. 183 Recent study by Horn et al. (2021) demonstrated the inhibitory properties of α-Cyperone on C. auris growth at a concentration of 150 μg/ml. 184 Their anti-fungal mechanism is yet to be elucidated. ...
Candida auris is an emerging, multi drug resistant fungal pathogen that has caused infectious outbreaks in over 45 countries since its first isolation over a decade ago, leading to in-hospital crude mortality rates as high as 72%. The fungus is also acclimated to disinfection procedures and persists for weeks in nosocomial ecosystems. Alarmingly, the outbreaks of C. auris infections in Coronavirus Disease-2019 (COVID-19) patients have also been reported. The pathogenicity, drug resistance and global spread of C. auris have led to an urgent exploration of novel, candidate antifungal agents for C. auris therapeutics. This narrative review codifies the emerging data on the following new/emerging antifungal compounds and strategies: antimicrobial peptides, combinational therapy, immunotherapy, metals and nano particles, natural compounds, and repurposed drugs. Encouragingly, a vast majority of these exhibit excellent anti- C. auris properties, with promising drugs now in the pipeline in various stages of development. Nevertheless, further research on the modes of action, toxicity, and the dosage of the new formulations are warranted. Studies are needed with representation from all five C. auris clades, so as to produce data of grater relevance, and broader significance and validity.
Lay summary:
Elimination of Candida auris that causes deadly infections to susceptible individuals is extremely challenging due to the lack of effective treatment options. Promising, new antifungal agents and strategies are being developed and further refinement will facilitate their clinical use in the near future.
... Nrf2 plays a critical role in preventing cell and tissue damage caused by oxidative stress. It controls the transcription of several cytoprotective genes in response to oxidative stress [56,57]. Previous studies have revealed that oxidative stress contributes to tendon degeneration and Nrf2/HO-1 The expression of COLI and COLIII was detected by immunohistochemistry assay in tendon injury. ...
Tendon stem cells (TSCs) are often exposed to oxidative stress at tendon injury sites, which impairs their physiological effect as well as therapeutic application. Recently, extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) were shown to mediate cell protection and survival under stress conditions. The function of BMSC-EVs may be affected by pretreatment with various factors such as eugenol (EUG)—a powerful antioxidant. In our previous study, we found that H2O2 significantly impaired TSC proliferation and tenogenic differentiation capabilities. Apoptosis and intracellular ROS accumulation in TSCs were induced by H2O2. However, such H2O2-induced damage was prevented by treatment with EUG-BMSC-EVs. Furthermore, EUG-BMSC-EVs activated the Nrf2/HO-1 pathway to counteract H2O2-induced damage in TSCs. In a rat patellar tendon injury model, the ROS level was significantly higher than that in the normal tendon and TSCs not pretreated showed a poor therapeutic effect. However, EUG-BMSC-EV-pretreated TSCs significantly improved tenogenesis and matrix regeneration during tendon healing. Additionally, the EUG-BMSC-EV group had a significantly improved fiber arrangement. Overall, EUG-BMSC-EVs protected TSCs against oxidative stress and enhanced their functions in tendon injury. These findings provide a basis for potential clinical use of EUG-BMSC-EVs as a new therapeutic vehicle to facilitate TSC therapies for tendon regeneration.
... Changes in the Bax/Bcl-2 ratio (i.e., index of the apoptotic potential of a cell [28] was evaluated, and AC effects were assessed by using its most effective concentration of 200 µg/mL. As shown in Figure 6, AC prevented the activation of caspase-3 and the up-regulated Bax/Bcl-2 ratio, known to be altered by H 2 O 2 treatment in SH-SY5Y cells [29] as well as in in vivo experimental models of ND [30]. Figure 5b,c, OS caused a huge increase in both ROS and MDA formation, whi however, completely prevented by AC. ...
Oxidative stress (OS) and the resulting reactive oxygen species (ROS) generation and inflammation play a pivotal role in the neuronal loss occurring during the onset of neurodegenerative diseases. Therefore, promising future drugs that would prevent or slow down the progression of neurodegeneration should possess potent radical-scavenging activity. Acacia catechu Willd. heartwood extract (AC), already characterized for its high catechin content, is endowed with antioxidant properties. The aim of the present study was to assess AC neuroprotection in both human neuroblastoma SH-SY5Y cells and rat brain slices treated with hydrogen peroxide. In SH-SY5Y cells, AC prevented a decrease in viability, as well as an increase in sub-diploid-, DAPI positive cells, reduced ROS formation, and recovered the mitochondrial potential and caspase-3 activation. AC related neuroprotective effects also occurred in rat brain slices as a reversal prevention in the expression of the main proteins involved in apoptosis and signalling pathways related to calcium homeostasis following OS-mediated injury. Additionally, unbiased quantitative mass spectrometry allowed for assessing that AC partially prevented the hydrogen peroxide-induced altered proteome, including proteins belonging to the synaptic vesicle fusion apparatus. In conclusion, the present results suggest the possibility of AC as a nutraceutical useful in preventing neurodegenerative diseases.
